Summary
We have undertaken molecular dynamics simulations on the d(CGCAAAAAAGCG)•d(CGCTTTTTTGCG) dodecamer in solution. In this study, we focus on aspects of conformation and dynamics, including the possibility of cross-strand hydrogen bonds. We compare our results with those from crystallography as well as infrared, Raman and NMR spectroscopy and cyclization kinetics. Our method of analysis allows us to visualise the curvature of the helix as a function of time during the simulation. We find that the major distortions of the helix axis path occur at the junctions between the (essentially straight) A-tract and the CG-and GC-tracts, although at one junction this is due to hyperflexibility (i.e., regions of high flexibility with no preferred direction of curvature), while at the other junction a static curvature is found (i.e., a preferred, sustained direction of curvature).
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References
Travers, A., Annu. Rev. Biochem., 58 (1989) 427.
Hagerman, P.J., Annu. Rev. Biochem., 59 (1990) 755.
Bolshoy, A., McNamara, P., Harrington, R.E. and Trifonov, E.N., Proc. Natl. Acad. Sci. USA, 88 (1991) 2312.
Ulanovsky, L., Bodner, M., Trifonov, E.N. and Choder, M., Proc. Natl. Acad. Sci. USA, 83 (1986) 862.
Trifonov, E.N. and Sussman, J.L., Proc. Natl. Acad. Sci. USA, 77 (1980) 3816.
Levene, S.D. and Crothers, D.M., J. Biomol. Struct. Dyn., 1 (1983) 429.
Wu, H.-M. and Crothers, D.M., Nature, 308 (1984) 509.
Coll, M., Frederick, C.A., Wang, A.H.-J. and Rich, A., Proc. Natl. Acad. Sci. USA, 84 (1987) 8385.
Nelson, H.C.M., Finch, J.T., Bonaventura, F.L. and Klug, A., Nature, 330 (1987) 221.
DiGabriele, A.D., Sanderson, M.R. and Steitz, T.A., Proc. Natl. Acad. Sci. USA, 86 (1989) 1816.
Fritsch, V. and Westhof, E., J. Am. Chem. Soc., 113 (1991) 8271.
Diekmann, S., Mazzarelli, J.M., McLaughlin, L.W., Von, Kitzing, E. and Travers, A.A., J. Mol. Biol., 225 (1992) 729.
Edwards, K.J., Brown, D.G., Spink, N., Skelly, J.V. and Neidle, S., J. Mol. Biol., 226 (1992) 1161.
Goodfellow, J.M. and Williams, M.A., Curr. Opin. Struct. Biol., 2 (1992) 211.
Van, Gunsteren, W.F. and Berendsen, H.J.C., Angew. Chem., Int. Ed. Engl., 29 (1990) 992.
MacCammon, J.A. and Harvey, S.C., Dynamics of Proteins and Nucleic Acids, Cambridge University Press, Cambridge, 1986.
Feuerstein, B.G., Pattabiraman, N. and Marton, L.J., Nucleic Acids Res., 17 (1989) 6883.
Herzyk, P., Neidle, S. and Goodfellow, J.M., J. Biomol. Struct. Dyn., 10 (1992) 97.
Boehncke, K., Nonella, M., Schulten, K. and Wang, A.H.-J., Biochemistry, 30 (1991) 5465.
Van, Gunsteren, W.F., Berendsen, H.J.C., Geurtsen, R.G. and Zwinderman, H.R.J., Ann. New York Acad. Sci., 482 (1986) 287.
Zielinski, T.J. and Shibata, M., Biopolymers, 29 (1990) 1027.
Seibel, G., Singh, U.C. and Kollman, P.A., Proc. Natl. Acad. Sci. USA, 82 (1985) 6537.
Singh, U.C., Weiner, S.J. and Kollman, P.A., Proc. Natl. Acad. Sci. USA, 82 (1985) 755.
Cruzeiro-Hansson, L., Swan, P.F., Pearl, L. and Goodfellow., J.M., Carcinogenesis, 13 (1992) 2067.
Parker, K., Cruzeiro-Hansson, L. and Goodfellow, J.M., J. Chem. Soc. Faraday Trans., 89 (1993) 2637.
Arnott, S., Chandrasekaran, R., Hall, I.H. and Puigjaner, L.C., Nucleic Acids Res., 2 (1983) 1493.
Weiner, S.J., Kollman, P.A., Case, D.A., Singh, U.C., Ghio, C., Alagona, G., ProfetaJr., S. and Weiner, P., J. Am. Chem. Soc., 106 (1984) 765.
Singh, U.C., Weiner, P.K., Caldwell, J. and Kollman, P.A., AMBER 3.0, University of California at San Francisco, San Francisco, CA, 1986.
Seibel, G.L., AMBER 3.0, Rev. A, University of California at San Francisco, San Francisco, CA, 1989.
Lavery, R. and Sklenar, H., J. Biomol. Struct. Dyn., 6 (1988) 63.
Lavery, R. and Sklenar, H., J. Biomol. Struct. Dyn., 6 (1989) 655.
Ravishanker, G., Swaminathan, S., Beveridge, D.L., Lavery, R. and Sklenar, H., J. Biomol. Struct. Dyn., 6 (1989) 669.
Saenger, W., Principles of Nucleic Acid Structure, Adenine Press, New York, NY, 1988.
Mohan, S. and Yathindra, M., J. Biomol. Struct. Dyn., 9 (1991) 113.
Elias, H.-G., Macromolecules, Vol. 1. Plenum Press, New York, NY, 1984, pp. 89–150.
Tanford, C., Physical Chemistry of Macromolecules, Wiley, New York, NY, 1961.
Bansal, M. and Bhattacharayya, D., In Sarma, R.H. and Sarma, M.H. (Eds.) Structure & Methods, Vol. 3, Adenine Press, New York, NY, 1990, pp. 139–153.
Gordon, A.L., Booth, E.D., Hunter, W.N. and Brown, T., Nucleic Acids Res., 20 (1992) 4753.
Taillandier, E., Ridoux, J.-P., Liquier, J., Leupin, W., Denny, W.A., Wang, Y., Thomas, G.A. and Peticolas, W.L., Biochemistry, 26 (1987) 3361.
Rao, S. and Kollman, P.A., J. Am. Chem. Soc., 107 (1985) 1611.
Brahms, S., Fritsch, V., Brahms, J.G. and Westhof, E., J. Mol. Biol., 223 (1992) 455.
Roy, S., Borah, B., Zon, G. and Cohen, J.S., Biopolymers, 26 (1987) 525.
Behling, R. and Kearns, D.R., Biochemistry, 25 (1986) 3335.
Tullius, T.D. and Dombroski, B.A., Science, 230 (1985) 679.
Burkhoff, A.M. and Tullius, T.D., Cell, 48 (1987) 935.
Price, M.A. and Tullius, T.D., Biochemistry, 32 (1993) 127.
Zhurkin, V.B., Gorin, A.A., Charakhchyan, A.A. and Ulyanov, N.B., In Beveridge, D. and Lavery, R. (Eds.) Theoretical Biochemistry and Molecular Biophysics, Vol. 1, Adenine Press, New York, NY, 1990, pp. 411–431.
Crothers, D.M., Drak, J., Kahn, J.D. and Levene, S.D., Methods Enzymol., 212 (1992) 3.
DiGabriele, A.D. and Steiz, T.A., J. Mol. Biol., 231 (1993) 1024.
Crothers, D.M., Haran, T.E. and Nadeau, J.G., J. Biol. Chem., 265 (1990) 7093.
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de Souza, O.N., Goodfellow, J.M. Molecular dynamics simulations of oligonucleotides in solution: Visualisation of intrinsic curvature. J Computer-Aided Mol Des 8, 307–322 (1994). https://doi.org/10.1007/BF00126748
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DOI: https://doi.org/10.1007/BF00126748